Gene-Activation Mechanisms in the Regression of Atherosclerosis, Elimination of Diabetes Type 2, and Prevention of Dementia

Abstract

Atherosclerotic vascular disease, diabetes mellitus (DM) and dementia are major global health problems. Both endogenous and exogenous factors activate genes functioning in biological processes. This review article focuses on gene-activation mechanisms that regress atherosclerosis, eliminate DM type 2 (DM2), and prevent cognitive decline and dementia. Gene-activating compounds upregulating functions of liver endoplasmic reticulum (ER) and affecting lipid and protein metabolism, increase ER size through membrane synthesis, and produce an antiatherogenic plasma lipoprotein profile. Numerous gene-activators regress atherosclerosis and reduce the occurrence of atherosclerotic disease. The gene-activators increase glucose disposal rate and insulin sensitivity and, by restoring normal glucose and insulin levels, remove metabolic syndrome and DM2. Patients with DM2 show an improvement of plasma lipoprotein profile and glucose tolerance together with increase in liver phospholipid (PL) and cytochrome (CYP) P450. The gene-activating compounds induce hepatic protein and PL synthesis, and upregulate enzymes including CYPs and glucokinase, nuclear receptors, apolipoproteins and ABC (ATP-binding cassette) transporters. They induce reparation of ER structures and eliminate consequences of ER stress. Healthy living habits activate mechanisms that maintain high levels of HDL and apolipoprotein AI, promote health, and prevent cognitive decline and dementia. Agonists of liver X receptor (LXR) reduce amyloid in brain plaques and improve cognitive performance in mouse models of Alzheimer`s disease. The gene activation increases the capacity to withstand cellular stress and to repair cellular damage and increases life span. Life free of major health problems and in good cognitive health promotes well-being and living a long and active life.

DNA Methylation Dynamics in Human Carotid Plaques After Cerebrovascular Events

“…19 Examples of POU2F1-regulated genes are the cytochrome P450 monooxygenases (CYP), which generate anti-inflammatory epoxy-fatty acid derivatives and the atheroprotective liver X receptor ligand oxysterol leading to ATP-binding cassette (ABC) cholesterol transporter activation. [20][21][22] Accordingly, the promoters of various CYP and ABC family genes were hypomethylated with increasing PCET, suggesting a release of transcriptional repression of these atheroprotective genes ( Table 2). Another example is the myocyte enhancer factor 2 C (MEF2C), a suppressor of the inflammatory response.…”

Alterations of LXRα and LXRβ expression in the hypothalamus of glucose-intolerant rats

“…LXR stimulation normalizes glycemia and improves insulin sensitivity in rodent models of type 2 diabetes and insulin resistance (Cao et al 2003, Laffitte et al 2003, Commerford et al 2007 while not affecting glycemia in nondiabetic animals (Cao et al 2003, Laffitte et al 2003. Thus, in recent years, LXRs have emerged as promising targets to treat diseases such as atherosclerosis and type 2 diabetes (Luoma 2011).…”

Why cancer survivors have a lower risk of Alzheimer disease

“…The authors interpreted their results as indicating that P-glycoprotein contributes to MDR1-related drug resistance, and that intrinsic and acquired Pgp regulations contribute to therapeutic failure and relapse in breast cancer [11]. Meanwhile a series of studies using several molecular biology approaches revealed additional data on the involvement of multidrug resistance and other mechanisms in Alzheimer or Parkinson disease, respectively [10][11][12][13][14][15][16][17][18][19][20][21]. For a recent review see [22].…”